Hmdb loader
Identification
HMDB Protein ID HMDBP13639
Secondary Accession Numbers None
Name Endonuclease 8-like 3
Synonyms
  1. DNA glycosylase FPG2
  2. DNA glycosylase/AP lyase Neil3
  3. Endonuclease VIII-like 3
  4. Nei-like protein 3
Gene Name NEIL3
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA) (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases (By similarity). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). No activity on 8-oxoG detected (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161).
Pathways
  • Base excision repair
Reactions Not Available
GO Classification
Biological Process
base-excision repair
interstrand cross-link repair
Cellular Component
nucleus
nucleoplasm
chromosome
Molecular Function
zinc ion binding
DNA-(apurinic or apyrimidinic site) lyase activity
bubble DNA binding
single-stranded DNA binding
double-stranded DNA binding
damaged DNA binding
DNA N-glycosylase activity
class I DNA-(apurinic or apyrimidinic site) endonuclease activity
MCM complex binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 606
Molecular Weight 67415.815
Theoretical pI 9.019
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q8K203
UniProtKB/Swiss-Prot Entry Name NEIL3_MOUSE
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  3. Torisu K, Tsuchimoto D, Ohnishi Y, Nakabeppu Y: Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease VIII-like protein. J Biochem. 2005 Dec;138(6):763-72. doi: 10.1093/jb/mvi168. [PubMed:16428305 ]
  4. Liu M, Bandaru V, Holmes A, Averill AM, Cannan W, Wallace SS: Expression and purification of active mouse and human NEIL3 proteins. Protein Expr Purif. 2012 Jul;84(1):130-9. doi: 10.1016/j.pep.2012.04.022. Epub 2012 May 5. [PubMed:22569481 ]
  5. Liu M, Bandaru V, Bond JP, Jaruga P, Zhao X, Christov PP, Burrows CJ, Rizzo CJ, Dizdaroglu M, Wallace SS: The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4925-30. doi: 10.1073/pnas.0908307107. Epub 2010 Feb 25. [PubMed:20185759 ]
  6. Hildrestrand GA, Neurauter CG, Diep DB, Castellanos CG, Krauss S, Bjoras M, Luna L: Expression patterns of Neil3 during embryonic brain development and neoplasia. BMC Neurosci. 2009 May 9;10:45. doi: 10.1186/1471-2202-10-45. [PubMed:19426544 ]
  7. Takao M, Oohata Y, Kitadokoro K, Kobayashi K, Iwai S, Yasui A, Yonei S, Zhang QM: Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant. Genes Cells. 2009 Feb;14(2):261-70. doi: 10.1111/j.1365-2443.2008.01271.x. Epub 2008 Jan 15. [PubMed:19170771 ]
  8. Sejersted Y, Hildrestrand GA, Kunke D, Rolseth V, Krokeide SZ, Neurauter CG, Suganthan R, Atneosen-Asegg M, Fleming AM, Saugstad OD, Burrows CJ, Luna L, Bjoras M: Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18802-7. doi: 10.1073/pnas.1106880108. Epub 2011 Nov 7. [PubMed:22065741 ]
  9. Regnell CE, Hildrestrand GA, Sejersted Y, Medin T, Moldestad O, Rolseth V, Krokeide SZ, Suganthan R, Luna L, Bjoras M, Bergersen LH: Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells. Cell Rep. 2012 Sep 27;2(3):503-10. doi: 10.1016/j.celrep.2012.08.008. Epub 2012 Sep 6. [PubMed:22959434 ]
  10. Rolseth V, Krokeide SZ, Kunke D, Neurauter CG, Suganthan R, Sejersted Y, Hildrestrand GA, Bjoras M, Luna L: Loss of Neil3, the major DNA glycosylase activity for removal of hydantoins in single stranded DNA, reduces cellular proliferation and sensitizes cells to genotoxic stress. Biochim Biophys Acta. 2013 May;1833(5):1157-64. doi: 10.1016/j.bbamcr.2012.12.024. Epub 2013 Jan 7. [PubMed:23305905 ]
  11. Liu M, Imamura K, Averill AM, Wallace SS, Doublie S: Structural characterization of a mouse ortholog of human NEIL3 with a marked preference for single-stranded DNA. Structure. 2013 Feb 5;21(2):247-56. doi: 10.1016/j.str.2012.12.008. Epub 2013 Jan 9. [PubMed:23313161 ]